A non-randomized pilot trial of the use of prazosin in the prevention of transition from acute stress disorder to post-traumatic stress disorder

Animal and human research suggests that the development of posttraumatic stress disorder (PTSD) may involve the overconsolidation of memories of a traumatic experience. Previous studies have attempted to use pharmaceutical agents, especially the β-adrenergic blocker propranolol, to reduce this overconsolidation. In this randomized, placebo-controlled study of the efficacy of propranolol in reducing the development of PTSD, we optimized dosages and conducted both psychophysiological and clinical assessments 1 and 3 months after the traumatic event. Forty-one emergency department patients who had experienced a qualifying acute psychological trauma were randomized to receive up to 240 mg/day of propranolol or placebo for 19 days. At 4 and 12 weeks post-trauma, PTSD symptoms were assessed. One week later, participants engaged in script-driven imagery of their traumatic event while psychophysiological responses were measured. Physiological reactivity during script-driven traumatic imagery, severity of PTSD symptoms, and the rate of the PTSD diagnostic outcome were not significantly different between the two groups. However, post hoc subgroup analyses showed that in participants with high drug adherence, at the 5-week posttrauma assessment, physiological reactivity was significantly lower during script-driven imagery in the propranolol than in the placebo subjects. The physiological results provide some limited support for a model of PTSD in which a traumatic conditioned response is reduced by posttrauma propranolol. However, the clinical results from this study do not support the preventive use of propranolol in the acute aftermath of a traumatic event.

BackgroundWe aimed to investigate the annual incidence of trauma and stress-related mental disorder including acute stress disorder (ASD) and post-traumatic stress disorder (PTSD) using the National Health Insurance Service Database. In addition, we estimated direct medical cost of ASD and PTSD in Korea.MethodsTo examine the incidence, we selected patients who had at least one medical claim containing a 10th revision of the International Statistical Classification of Diseases and Related Health Problems code for ASD (F43.0) and PTSD (F43.1) and had not been diagnosed in the previous 360 days, from 2010 to 2017. We estimated annual incidence and the number of newly diagnosed patients of ASD and PTSD. Annual prevalence and direct medical cost of ASD and PTSD were also estimated.ResultsThe number of newly diagnosed cases of ASD and PTSD from 2011 to 2017 totaled 38,298 and 21,402, respectively. The mean annual incidence of ASD ranged from 8.4 to 13.7 per 100,000 population and that of PTSD ranged from 4.2 to 8.3 per 100,000 population, respectively. The incidence of ASD was found more in females and was highest among the 70–79 years of age group and the self-employed individuals group. The incidence of PTSD was also more common in the female group. However, the incidence of PTSD was highest in the 60–69 years of age group and in the medical aid beneficiaries group. The annual estimated medical cost per person of ASD ranged from 104 to 149 US dollars (USD). In addition, that of PTSD ranged from 310 to 426 USD.ConclusionFrom 2011 to 2017, the annual incidence and direct medical cost of ASD and PTSD in Korea were increased. Proper information on ASD and PTSD will not only allows us to accumulate more knowledge about these disorders themselves but also lead to more appropriate therapeutic interventions by improving the ability to cope with these trauma related psychiatric sequelae.

The authors aim to delineate cognitive dysfunction associated with posttraumatic stress disorder (PTSD) by evaluating a well-defined cohort of former World War II prisoners of war (POWs) with documented trauma and minimal comorbidities. The authors studied a cross-sectional assessment of neuropsychological performance in former POWs with PTSD, PTSD with other psychiatric comorbidities, and those with no PTSD or psychiatric diagnoses. Participants who developed PTSD had average IQ, while those who did not develop PTSD after similar traumatic experiences had higher IQs than average (approximately 116). Those with PTSD performed significantly less well in tests of selective frontal lobe functions and psychomotor speed. In addition, PTSD patients with co-occurring psychiatric conditions experienced impairment in recognition memory for faces. Higher IQ appears to protect individuals who undergo a traumatic experience from developing long-term PTSD, while cognitive dysfunctions appear to develop with or subsequent to PTSD. These distinctions were supported by the negative and positive correlations of these cognitive dysfunctions with quantitative markers of trauma, respectively. There is a suggestion that some cognitive decrements occur in PTSD patients only when they have comorbid psychiatric diagnoses.

The objective of this study was to explore whether ketamine prevents or exacerbates acute or post-traumatic stress disorders in military trauma patients. We conducted a retrospective study of a database from the French Military Health Service, including all soldiers surviving a war injury in Afghanistan (2010-2012). The diagnosis of post-traumatic stress disorder was made by a psychiatrist and patients were analysed according to the presence or absence of this condition. Analysis included the following covariables: age; sex; acute stress disorder; blast injury; associated fatality; brain injury; traumatic amputation; Glasgow coma scale; injury severity score; administered drugs; number of surgical procedures; physical, neurosensory or aesthetic sequelae; and the development chronic pain. Covariables related to post-traumatic and acute stress disorders with a p≤0.10 were included in a multivariable logistic regression model. The data from 450 soldiers were identified; 399 survived, of which 274 were analysed. Among these, 98 (36%) suffered from post-traumatic stress disorder and 89 (32%) had received ketamine. Fifty-four patients (55%) in the post-traumatic stress disorder group received ketamine vs. 35 (20%) in the no PTSD group (p<0.001). The 89 injured soldiers who received ketamine had a median (IQR [range]) injury severity score of 5 (3-13 [1-26]) vs. 3 (2-4 [1-6] in the 185 patients who did not (p<0.001). At multivariable analysis, only acute stress disorder and total number of surgical procedures were independently associated with the development of post-traumatic stress disorder. In this retrospective study, ketamine administration was not a risk factor for the development of post-traumatic stress disorder in the military trauma setting.

Pharmacological prevention of post-traumatic stress disorder and acute stress disorder: a systematic review and meta-analysis

Treatment of traumatic birth experience with postpartum early eye movement desensitization and reprocessing therapy: a randomized clinical trial.

In a group of crime victims recruited from the community, the authors investigated the ability of both a diagnosis of acute stress disorder and its component symptoms to predict posttraumatic stress disorder (PTSD) at 6 months. A mixed-sex group of 157 victims of violent assaults were interviewed within 1 month of the crime. At 6-month follow-up 88% were reinterviewed by telephone and completed further assessments generating estimates of the prevalence of PTSD. The rate of acute stress disorder was 19%, and the rate of subsequent PTSD was 20%. Symptom clusters based on the DSM-IV criteria for acute stress disorder were moderately strongly interrelated. All symptom clusters predicted subsequent PTSD, but not as well as an overall diagnosis of acute stress disorder, which correctly classified 83% of the group. Similar predictive power could be achieved by classifying the group according to the presence or absence of at least three reexperiencing or arousal symptoms. Logistic regression indicated that both a diagnosis of acute stress disorder and high levels of reexperiencing or arousal symptoms made independent contributions to predicting PTSD. This exploratory study provides evidence for the internal coherence of the new acute stress disorder diagnosis and for the symptom thresholds proposed in DSM-IV. As predicted, acute stress disorder was a strong predictor of later PTSD, but similar predictive power may be possible by using simpler criteria.

Recent Data Lead to Shift in PTSD Criteria

PTSD and Combat-Related Injuries: Functional Neuroanatomy

Acute stress disorder and posttraumatic stress disorder (PTSD) are debilitating psychiatric conditions that may occur following traumatic events or severe stressors. Generally, these two conditions have similar diagnostic criteria, with acute stress disorder marked by symptoms for less than 1 month and PTSD with symptoms lasting 1 month or more. The exact mechanism by which PTSD develops in the brain is not known. Groups at risk for developing PTSD include women, people with low socioeconomic status, previously married people, and people younger than 65 years. Symptoms must include exposure to a stressor, intrusive thoughts or perceptions, avoidance, negative cognitions or emotions, and marked arousal and reactivity. Early treatment of acute stress disorder may prevent progression to PTSD. Treatment is primarily trauma-based psychotherapy, although medications may be used for symptom management and treating comorbid psychiatric conditions such as depression or panic attacks. Patients with PTSD should not be treated with benzodiazepines due to worsening morbidity. Treatment of PTSD limits the course of the condition and reduces comorbidities.

Intravenous Ketamine Exacerbating Symptoms of Acute Stress Disorder: A Case Report and Systematized Review of Existing Literature

The utility of the acute stress disorder diagnosis to describe acute stress reactions and predict subsequent posttraumatic stress disorder (PTSD) was evaluated. A systematic search was conducted in the PsycINFO, MEDLINE, and PubMed databases for English-language articles published between 1994 and 2009 using keywords that combined acute stress disorder and posttraumatic stress disorder. Studies were selected that assessed for acute stress disorder within 1 month of trauma exposure and assessed at a later time for PTSD, using established measures of acute stress disorder and PTSD. For each study, capacity of the acute stress disorder diagnosis to predict PTSD was calculated in terms of sensitivity, specificity, and positive and negative predictive power. For studies that reported subsyndromal acute stress disorder, the same analyses were calculated for cases that initially satisfied subsyndromal acute stress disorder criteria. Twenty-two studies were identified as suitable for analysis (19 with adults and 3 with children). Diagnosis of acute stress disorder resulted in half the rate of distressed people in the acute phase being identified relative to including cases with subsyndromal acute stress disorder. In terms of prediction, the acute stress disorder diagnosis had reasonable positive predictive power (proportion of people with acute stress disorder who later developed PTSD). In contrast, the sensitivity (proportion of people who developed PTSD who initially met criteria for acute stress disorder) was poor. The acute stress disorder diagnosis does not adequately identify the majority of people who will eventually develop PTSD. There is a need to formally describe acute stress reactions, but this goal may be achieved more usefully by describing the broad range of initial reactions rather than by attempting to predict subsequent PTSD.

IntroductionThe aim of this study was to investigate the neurofunctional alterations in both acute and chronic post‐traumatic stress disorder (PTSD) resulting from the same stress experience.MethodsBrain responses to emotional trauma‐related and neutral pictures with a symptom provocation task were measured using functional magnetic resonance imaging (fMRI). Twenty‐four PTSD patients resulting from a mining accident and 14 controls exposed to the same accident without PTSD two months post‐trauma were recruited. In the follow‐up study 20 PTSD patients and 14 controls were also recruited after 24 months post‐trauma. Correlations were conducted in PTSD between altered fMRI blood oxygenation level‐dependent (BOLD) signals of areas extracted as regions of interest and three Clinician‐Administered PTSD Scale (CAPS) subscores respectively.ResultsIn response to picture stimulus (traumatic negative pictures versus neutral pictures), the acute PTSD group showed greater activation in the bilateral posterior cingulate gyri, left precuneus, right fusiform and left parahippocampal gyrus than the chronic PTSD group (P &lt; 0.001, cluster size &gt; 20 voxels). In the acute PTSD group, BOLD signals of either posterior cingulate gyrus correlated positively with CAPS intrusion subscores. There was also no significant correlation between BOLD signals of five regions mentioned above in the chronic PTSD group and three CAPS subscores.DiscussionThese findings suggested that brain circuits affected in acute PTSD may be more extended than chronic PTSD. The reason may due to the formation of traumatic memory in the acute phase of PTSD.

Over 7 million Americans are affected by post‐traumatic stress disorder (PTSD), a debilitating mental illness that is associated with significant cardiovascular disease risk. Women are twice as likely as men to develop PTSD after a traumatic event. A prior study from our laboratory showed that sympathetic nervous system reactivity during combat related and non‐combat related stress is heightened in PTSD; however, this study was conducted in a predominantly male cohort and did not consider the potential influence of sex on neural cardiovascular function in PTSD. The aim of the current study was to determine if women with PTSD have heightened blood pressure (BP), heart rate (HR), and sympathetic reactivity to acute mental stress than men with PTSD. We recruited 15 women and 18 men clinically diagnosed with PTSD and confirmed using the Clinician Administered PTSD Scale (CAPS) and PTSD Checklist‐Military (PCL‐M) surveys. We measured muscle sympathetic nerve activity (MSNA), continuous BP, HR and heart rate variability (HRV) at baseline and during 3 minutes of mental arithmetic. Women and men were matched for race, age (41±2 vs 38±2 years, p=0.191), body mass index (31±2 vs 29±2 kg/m2, p=0.368), CAPS (71 ±9 vs 74 ±4, p=0.732) and PCLM (57 ±5 vs 68 ±4, p=0.129) scores. Likewise, baseline systolic BP (131±5 vs 128±4 mmHg), diastolic BP (76±4 vs 74±2 mmHg) and HR (70±3 vs 64±2 beats/min) were comparable (P&gt;0.05) between women and men. Although resting HRV measures were not different between groups (p&gt;0.05), resting MSNA was higher (p=0.008) in women compared to men (27±3 vs 16±3 bursts/min). In response to mental arithmetic, systolic BP reactivity was higher in women compared to men (Δ+5.1±1 versus Δ+2.2±1 mm Hg, p&lt;0.001). Diastolic BP (p=0.366) and HR (p=0.170) responses were not different. However, MSNA reactivity was higher (p=0.04) in women compared to men (Δ15.2±5 versus Δ6.4±3 bursts/min), suggesting an exaggerated sympathetic response to acute stress. Although RMSSD reactivity was similar between both groups (p=0.347), HF response to mental stress was blunted (p=0.05) in women compared to men, suggesting a greater withdrawal of parasympathetic control of the heart during acute stress. In summary, women with PTSD show an exaggerated blood pressure and sympathetic response to acute mental stress coupled with a blunted parasympathetic control of the heart. These results provide important insight into the physiological mechanisms linking the high risk of PTSD in women and the associated cardiovascular disease and hypertension risk.Support or Funding InformationThis work was supported by National Institutes of Health (NIH) Grant R01 HL135183; NIH R61 AT010457, VA Merit I01CX001065, the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Decatur, Georgia, and the APS STRIDE Undergraduate Summer Research Fellowship, grant program number NHLBI; 1 R25 HL115473‐01.

This study addresses the extent to which DSM-IV and DSM-5 definitions of acute stress disorder (ASD) predict subsequent posttraumatic stress disorder (PTSD) and related psychiatric disorders following trauma. Patients with randomized admissions to 5 hospitals across Australia (N = 596) were assessed in hospital and reassessed for PTSD at 3 (n = 508), 12 (n = 426), 24 (n = 439), and 72 (n = 314) months using the Clinician-Administered PTSD Scale; DSM-IV definition of PTSD was used at each assessment, and DSM-5 definition was used at 72 months. The Mini-International Neuropsychiatric Interview (MINI) was used at each assessment to assess anxiety, mood, and substance use disorders. Forty-five patients (8%) met DSM-IV criteria, and 80 patients (14%) met DSM-5 criteria for ASD. PTSD was diagnosed in 93 patients (9%) at 3, 82 patients (10%) at 12, 100 patients (12%) at 24, and 26 patients (8%) at 72 months; 19 patients (6%) met DSM-5 criteria for PTSD at 72 months. Comparable proportions of those diagnosed with ASD developed PTSD using DSM-IV (3 months = 46%, 12 months = 39%, 24 months = 32%, and 72 months = 25%) and DSM-5 (43%, 42%, 33%, and 24%) ASD definitions. Sensitivity was improved for DSM-5 relative to DSM-IV for depression (0.18 vs 0.30), panic disorder (0.19 vs 0.41), agoraphobia (0.14 vs 0.40), social phobia (0.12 vs 0.44), specific phobia (0.24 vs 0.58), obsessive-compulsive disorder (0.17 vs 0.47), and generalized anxiety disorder (0.20 vs 0.47). More than half of participants with DSM-5-defined ASD had a subsequent disorder. The DSM-5 criteria for ASD results in better identification of people who will subsequently develop PTSD or another psychiatric disorder relative to the DSM-IV criteria. Although prediction is modest, it suggests that the new ASD diagnosis can serve a useful function in acute trauma settings for triaging those who can benefit from either early intervention or subsequent monitoring.